Solitary fibrous tumour of the parotid gland.
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Child↗
Biomedical subjects
J Stewart
Publications and source records attributed to J Stewart.
Neurotensin analog selective for hypothermia over antinociception and exhibiting atypical neuroleptic-like properties.
Neurotensin (NT) is a tridecapeptide neurotransmitter in the central nervous system. It has been implicated in the therapeutic effects of neuroleptics. Central activity of NT can only be demonstrated by direct injection into the brain, since it is readily degraded by peptidases in the periphery. We have developed many NT(8-13) analogs that are resistant to peptidase degradation and can cross the blood-brain barrier (BBB). In this study, we report on one of these analogs, NT77L. NT77L induced hypothermia (ED(50)=6.5 mg/kg, i.p.) but induced analgesia only at the highest dose examined (20 mg/kg, i.p.). Like the atypical neuroleptic clozapine, NT77L blocked the climbing behavior in rats induced by the dopamine agonist apomorphine (600 microg/kg) with an ED(50) of 5.6 mg/kg (i.p.), without affecting the licking and the sniffing behaviors. By itself NT77L did not cause catalepsy, but it moderately reversed haloperidol-induced catalepsy with an ED(50) of 6.0 mg/kg (i.p.). Haloperidol alone did not lower body temperature, but it potentiated the body temperature lowering effect of NT77L. In studies using in vivo microdialysis NT77L showed similar effects on dopamine turnover to those of clozapine, and significantly different from those of haloperidol in the striatum. In the prefrontal cortex, NT77L significantly increased serotonergic transmission as evidenced by increased 5-hydroxyindole acetic acid:5-hydroxytryptamine (5-HIAA:5-HT) ratio. Thus, NT77L selectively caused hypothermia, over antinociception, while exhibiting atypical neuroleptic-like effects.
Analgesics↗
Mechanism of processivity clamp opening by the delta subunit wrench of the clamp loader complex of E. coli DNA polymerase III.
The dimeric ring-shaped sliding clamp of E. coli DNA polymerase III (beta subunit, homolog of eukaryotic PCNA) is loaded onto DNA by the clamp loader gamma complex (homolog of eukaryotic Replication Factor C, RFC). The delta subunit of the gamma complex binds to the beta ring and opens it. The crystal structure of a beta:delta complex shows that delta, which is structurally related to the delta' and gamma subunits of the gamma complex, is a molecular wrench that induces or traps a conformational change in beta such that one of its dimer interfaces is destabilized. Structural comparisons and molecular dynamics simulations suggest a spring-loaded mechanism in which the beta ring opens spontaneously once a dimer interface is perturbed by the delta wrench.
Amino Acid Sequence↗
Changing risk behaviours for non-communicable disease in New Zealand working men--is workplace intervention effective?
AIMS: To evaluate the effectiveness of a health promotion programme targeting dietary behaviours and physical activity among male hourly-paid workers and to explore demographic and attitudinal influences on dietary patterns at baseline. METHODS: A controlled field trial compared workers at one intervention and one control worksite. The intervention comprised nutrition displays in the cafeteria and monthly 30-minute workshops for six months. Key outcome measures at six and twelve-months were self-reported dietary and lifestyle behaviours, nutrition knowledge, body mass index (BMI), waist circumference and blood pressure. RESULTS: 132 men at the intervention site and 121 men at the control site participated in the study and a high retention rate (94% at 6-months and 89% at 12-months) was achieved. At baseline, 40% of the total sample (253) were obese, 30% had elevated blood pressure, 59% indicated an excessive fat intake and 92% did not meet the recommended vegetable and fruit intake. The intervention reduced fat intake, increased vegetable intake and physical activity, improved nutrition knowledge and reduced systolic blood pressure when compared to the control site. There was no difference in change in mean BMI or waist circumference. Reduction in BMI was associated with reduction in fat intake. DISCUSSION: Low intensity workplace intervention can significantly improve reported health behaviours and nutrition knowledge although the impact on more objective measures of risk was variable. A longer duration or more intensive intervention may be required to achieve further reduction in risk factors.
Adult↗
The application of comparative genomic hybridization as an additional tool in the chromosome analysis of acute myeloid leukemia and myelodysplastic syndromes.
In acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) there are frequently complex karyotypes with multiple structurally altered chromosomes, many of which are marker chromosomes of unknown origin. The aim of this study was to apply comparative genomic hybridization (CGH) to cases of AML or MDS in transformation submitted for routine cytogenetic analysis to investigate whether this approach would yield any further information and, if possible, to predict which cases would benefit from CGH analysis. Nineteen cases with AML or MDS in transformation were analyzed. CGH revealed nine cases with gains or losses of chromosomal material. In six of these cases the chromosomal location of this material was not apparent from cytogenetic analysis especially when multiple markers were present. By using fluorescence in situ hybridization (FISH) with specific libraries for the chromosome regions that showed discordance between CGH and conventional cytogenetics, we were able to identify the chromosome location of material within the karyotype. In this group of six patients, four cases of an unbalanced translocation involving regions of chromosomes 5 and 17 were characterized. Three of these cases had additional abnormalities, including two cases with regions of amplification in which oncogenes are located (MYC, MLL) and one case with a dic(7;21)(p10;p10). In all six cases it was possible to characterize complex chromosomal aberrations such as derivative chromosomes, marker chromosomes, and ring chromosomes. This study demonstrates that CGH can detect true gain and loss of critical chromosome regions more accurately than conventional karyotyping in cases with very complex karyotypes, and can thus prove useful in predicting prognosis and pinpointing areas of the genome that require further study. Also, CGH can be a useful technique to identify the origin of marker chromosomes, and it can assist in choice of probes for confirmatory FISH, when there is no clue provided from the analysis of G-banded chromosomes.
Acute Disease↗
Involvement of apolipoprotein E in herpes simplex encephalitis.
APOE polymorphism may influence risk for cold sores and, by interacting with latent HSV-1, risk for Alzheimer's disease (AD). APOE genotype also influences outcome after brain injury. We sought to determine whether APOE genotype influences risk for herpes simplex encephalitis (HSE), whether apoE is involved in the response to HSE and if APOE genotype influences outcome from HSE. There was increased immunoreactivity of neurons, neuropil and glia for apoE areas of brain damaged by HSE. APOE genotypes for cases of HSE (n = 57) were similar to those of controls (n = 41). APOE genotypes for survivors of HSE were similar to those of patients who died. We conclude that apoE is involved in the response to damage associated with HSE, as in other forms of brain injury. However, APOE genotype does not appear to influence either the risk of developing HSE or subsequent mortality.
Adolescent↗
Mechanism of beta clamp opening by the delta subunit of Escherichia coli DNA polymerase III holoenzyme.
The beta sliding clamp encircles the primer-template and tethers DNA polymerase III holoenzyme to DNA for processive replication of the Escherichia coli genome. The clamp is formed via hydrophobic and ionic interactions between two semicircular beta monomers. This report demonstrates that the beta dimer is a stable closed ring and is not monomerized when the gamma complex clamp loader (gamma(3)delta(1)delta(1)chi(1)psi(1)) assembles the beta ring around DNA. delta is the subunit of the gamma complex that binds beta and opens the ring; it also does not appear to monomerize beta. Point mutations were introduced at the beta dimer interface to test its structural integrity and gain insight into its interaction with delta. Mutation of two residues at the dimer interface of beta, I272A/L273A, yields a stable beta monomer. We find that delta binds the beta monomer mutant at least 50-fold tighter than the beta dimer. These findings suggest that when delta interacts with the beta clamp, it binds one beta subunit with high affinity and utilizes some of that binding energy to perform work on the dimeric clamp, probably cracking one dimer interface open.
Adenosine Triphosphate↗
Modulation of food intake by the kappa opioid U-50,488H: evidence for an effect on satiation.
The main goal of the present study was to test the hypothesis that the prophagic effect of the kappa opioid agonist U-50,488H (U50) is primarily due to an effect on satiation. In Experiment 1, the feeding effects of U50 (2.0 and 4.0 mg/kg, i.p.) was tested in animals with ad libitum access to ground food and to three sucrose solutions (1, 4, and 20%). In Experiment 2, a classical "one-bottle" test was utilized to test for the effect of U50 (4.0 mg/kg, i.p.) on the intake of five different sucrose solutions (1, 4, 16, 32, and 40%) over a 30-min period. Finally, in Experiment 3 we evaluated the effect of U50 (2.0, 4.0, and 6.0 mg/kg, i.p.) on extracellular dopamine (DA) concentration in the nucleus accumbens. In Experiment 1, U50 enhanced the intake of ground food but not of sucrose. In Experiment 2, U50 increased the intake of high concentration sucrose solutions whereas it decreased that of low concentration solutions. In Experiment 3, U50 produced a dose-dependent decrease in DA concentrations in the absence but not in the presence of food. The most likely explanation for the present results is that U50 enhances feeding by activating mechanisms that block satiety and satiation. In contrast, we found little evidence for an effect of U50 on palatability.
3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
A role for the CRF-containing pathway from central nucleus of the amygdala to bed nucleus of the stria terminalis in the stress-induced reinstatement of cocaine seeking in rats.
RATIONALE: We reported previously that bilateral injection of a corticotropin-releasing factor (CRF)-receptor antagonist, D-Phe CRF(12-41), into the bed nucleus of the stria terminalis (BNST) blocks the reinstatement of cocaine seeking induced by footshock, whereas the injection of CRF into the same region induces reinstatement. One source of CRF in the BNST arises from a CRF-containing projection originating in the central nucleus of the amygdala (CeA). OBJECTIVE: To determine whether the CRF-containing projection from the amygdala to the BNST is involved in the mediation of stress-induced reinstatement of cocaine seeking by functionally interrupting the pathway. METHODS: Rats trained to self-administer cocaine (1 mg/kg, IV, 9 days) were given extinction sessions after a 10- to 11-day drug-free period, followed by tests for stress-induced reinstatement (footshock: 15 min intermittent 0.8-mA footshocks given immediately before presentation of the previously active lever). Before the tests, animals were pretreated with either: (1) TTX (2.5 ng) in amygdala (including the CeA) in one hemisphere and D-Phe CRF(12-41) (50 ng) in BNST in the other, (2) unilateral TTX, or (3) unilateral D-Phe. RESULTS: Footshock reinstated cocaine seeking following unilateral injections of either TTX in amygdala or D-Phe in BNST, but following the injection of both TTX in amygdala and D-Phe in BNST the effects of footshock were greatly attenuated. CONCLUSION: These results suggest that the CRF-containing pathway from CeA to BNST is involved in mediating the effects of CRF and its receptor antagonist in the BNST on the reinstatement of cocaine seeking.
Amygdala↗
Utility of urinary cytology for diagnosing human polyoma virus infection in transplant recipients: a study of 37 cases with electron microscopic analysis.
Human polyoma virus (HPOV) infection is associated with hemorrhagic cystitis, tubulointerstitial nephritis, and renal transplant dysfunction/allograft loss. We evaluated the utility of cytologic examination to detect HPOV infection in 37 urinary cytology (UC) samples (3 bladder washings, and 34 voided samples) from 29 transplant patients, compared to electron microscopic studies (EMS). Evidence of viral infection was found in 11 specimens (30%). Five cases were diagnosed as HPOV by both UC and EMS. One was positive for HPOV by EMS only. Two cases diagnosed as HPOV by UC were demonstrated to be adenovirus (AV) with EMS. Two cases diagnosed as cytomegalovirus (CMV) by EMS had negative UC. One was called HPOV by UC; EMS in this case was negative. Compared to EMS, the sensitivity and specificity of UC for detecting HPOV were 83% and 90%, respectively, with a positive predictive value of 63% and a negative predictive value of 96%. We conclude that UC is a relatively sensitive and specific method for detecting active HPOV infection in transplant patients, and is important in light of the clinical significance of HPOV infection in transplant recipients. The sensitivity and accuracy of UC for diagnosing HPOV can be increased by adding EMS.
Adenoviridae↗
Carriage of Neisseria meningitidis among household contacts of patients with meningococcal disease in New Zealand.
The aims of this study were to estimate carriage prevalence, identify factors predictive of carriage, and compare strains of Neisseria meningitidis isolated from patients with meningococcal disease and their household contacts. A total of 954 contacts of 160 patients had a nasopharyngeal swab and an interview relating to factors associated with carriage. The carriage prevalence was 20.4% for Neisseria meningitidis, 11.3% for serogroup B, and 2.6% for serogroup C. Age-standardised carriage was higher in Maori (36.8%) than in Pacific Island (21.5%) or European/other (11.1%) ethnic groups. Factors associated with carriage were smoking, with personal smokers (odds ratio [OR] 2.5) and passive smokers (OR 1.6) having a higher carriage risk than those in smoke-free houses; ethnicity, with Maoris having a higher carriage risk than those of non-Maori or non-Pacific Island ethnicity (OR 2.2); gender, with males at higher risk than females (OR 1.7); and age, with 0-4-year-olds less likely and 15-24-year-olds more likely to be carriers than those over 25 years. Strong patient-contact clustering by meningococcal strain (chi-square1 = 16.7, P=0.00004) suggested an important role for the household setting in transmission. The low carriage prevalence of serogroup B Neisseria meningitidis among household contacts may reflect its low transmissibility but high virulence. No direct relationship was found between prevalence of ethnic-specific carriage and the incidence of meningococcal disease.
Adolescent↗
Identification of two putative ATP-cassette genes in Encephalitozoon intestinalis.
Currently existing chemotherapeutic compounds are limited and few are effective for treating microsporidiosis. It is possible that resistance of Encephalitozoon to some drugs occurs by efflux mechanisms similar to those previously described for mammalian tumour cells, bacteria or protozoal parasites such as Plasmodium, Leishmania and Entamoeba histolytica. The data in the present study suggest that Encephalitozoon intestinalis contains at least one multidrug resistance gene. We report here two complete sequences EiABC1 and EiABC2, encoding different ATP-binding cassette genes from E. intestinalis, including a P-gp.
ATP-Binding Cassette Transporters↗
Drug-induced reinstatement to heroin and cocaine seeking: a rodent model of relapse in polydrug use.
The authors investigated several features of polydrug use in rats. Heroin and cocaine were self-administered following responses on different levers, with only 1 drug and 1 lever available on alternate days of training. Four doses of each drug (heroin: 25, 50, 100, and 200 microg/kg/infusion; cocaine: 0.25, 0.5, 1, and 2 mg/kg/infusion) were tested, and each rat was exposed to a single dose combination. Rats readily developed drug-specific and dose-related responding. During extinction, rats displayed a significant bias for responding on the cocaine- associated lever. Priming injections of either cocaine (20 mg/kg) or heroin (0.25 mg/kg) reinstated responding that was selective for the lever previously associated with each drug. These results suggest that in this type of polydrug use, drugs have the capacity to activate drug-seeking behavior selectively oriented toward stimuli previously associated with their administration.
Animals↗
Minimum information about a microarray experiment (MIAME)-toward standards for microarray data.
Microarray analysis has become a widely used tool for the generation of gene expression data on a genomic scale. Although many significant results have been derived from microarray studies, one limitation has been the lack of standards for presenting and exchanging such data. Here we present a proposal, the Minimum Information About a Microarray Experiment (MIAME), that describes the minimum information required to ensure that microarray data can be easily interpreted and that results derived from its analysis can be independently verified. The ultimate goal of this work is to establish a standard for recording and reporting microarray-based gene expression data, which will in turn facilitate the establishment of databases and public repositories and enable the development of data analysis tools. With respect to MIAME, we concentrate on defining the content and structure of the necessary information rather than the technical format for capturing it.
Computational Biology↗
Treatment satisfaction and psychological well-being with insulin glargine compared with NPH in patients with Type 1 diabetes.
AIMS: To assess satisfaction with treatment and psychological well-being associated with insulin glargine and Neutral Protamine Hagedorn (NPH). Insulin glargine, a new long-acting insulin analogue, provides constant, peakless insulin release following once-daily administration and is associated with fewer hypoglycaemic episodes, despite metabolic control equivalent to that achieved with NPH human basal insulin. METHODS: The Diabetes Treatment Satisfaction Questionnaire (DTSQ) and Well-being Questionnaire (W-BQ) were completed at baseline and at weeks 8, 20 or 28 by 517 patients with Type 1 diabetes participating in a randomized, controlled European trial comparing insulin glargine and NPH. Analysis of covariance was performed on change from baseline scores (main effects: treatment and pooled site; covariate: baseline scores). RESULTS: Treatment satisfaction improved with insulin glargine at all time points, including endpoint, but deteriorated slightly with NPH. These differences were significant throughout the study (change from baseline to endpoint: +1.27 vs. -0.56; P = 0.0001). Outcomes were better with insulin glargine for the DTSQ items, Perceived Frequency of Hyperglycaemia and Hypoglycaemia, with statistically significant differences at week 28 and endpoint for hyperglycaemia (P = 0.0373 and 0.0379) and at week 20 for hypoglycaemia (P = 0.0024). There was no difference in psychological well-being between the treatment groups, with mean scores increasing in both. CONCLUSIONS: Study participants had treatment-independent improvements in General Well-being. Advantages for insulin glargine were seen in significantly improved Treatment Satisfaction throughout the study, together with lower Perceived Frequency of Hyperglycaemia than for patients on NPH, without a significant increase in Perceived Frequency of Hypoglycaemia.
Adolescent↗
Giant Merkel cell carcinoma involving the upper extremity.
We report a case of Merkel cell carcinoma involving the upper extremity that exceeded 23 cm x 18 cm in size. To the best of our knowledge, this represents the largest tumor of this type reported.
Aged↗
Effect of computer support on younger women with breast cancer.
OBJECTIVE: Assess impact of a computer-based patient support system on quality of life in younger women with breast cancer, with particular emphasis on assisting the underserved. DESIGN: Randomized controlled trial conducted between 1995 and 1998. SETTING: Five sites: two teaching hospitals (Madison, Wis, and Chicago, Ill), two nonteaching hospitals (Chicago), and a cancer resource center (Indianapolis, Ill). The latter three sites treat many underserved patients. PARTICIPANTS: Newly diagnosed breast cancer patients (N = 246) under age 60. INTERVENTIONS: Experimental group received Comprehensive Health Enhancement Support System (CHESS), a home-based computer system providing information, decision-making, and emotional support. MEASUREMENTS AND MAIN RESULTS: Pretest and two post-test surveys (at two- and five-month follow-up) measured aspects of participation in care, social/information support, and quality of life. At two-month follow-up, the CHESS group was significantly more competent at seeking information, more comfortable participating in care, and had greater confidence in doctor(s). At five-month follow-up, the CHESS group had significantly better social support and also greater information competence. In addition, experimental assignment interacted with several indicators of medical underservice (race, education, and lack of insurance), such that CHESS benefits were greater for the disadvantaged than the advantaged group. CONCLUSIONS: Computer-based patient support systems such as CHESS may benefit patients by providing information and social support, and increasing their participation in health care. These benefits may be largest for currently underserved populations.
Adult↗
Flexible cystoscopy: is the volume and content of the urethral gel critical?
PURPOSE: To determine whether volume (10 or 20mL) or the presence of 2% lidocaine (lignocaine) in the gel used for urethral lubrication alters the discomfort felt during flexible cystoscopy. PATIENTS AND METHODS: A randomized double-blind trial was performed in men attending for flexible cystoscopy. Patients were assigned to one of four groups: 10 mL of gel with or without lidocaine and 20 mL with or without lidocaine. Gel was retained for 10 minutes prior to cystoscopy. Pain felt during both the instillation of the gel and the cystoscopy itself was evaluated using a visual analog scale (0-10). RESULTS: Interim analysis after 147 patients had been recruited revealed a significant difference between the groups in terms of the pain felt on instillation of the gel, leading to an early termination of the trial. There was a significant reduction in pain on cystoscopy in patients receiving 20 mL of gel if this contained lidocaine. CONCLUSION: The least pain on cystoscopy occurred in patients receiving 20 mL of gel containing lidocaine.
Aged↗